Despite advances in techniques of resuscitation, cardiac arrest and related cardiac problems are associated with significant morbidity and mortality. Moreover, due to the incidence of sudden cardiac death (“SCD”) and other life threatening cardiac ailments, cardiac dysfunction remains a major public health problem, especially for developed countries. For example, it is estimated that between 250,000 and 300,000 SCDs occur per year in the United States; an undoubtedly conservative estimate due to the fact that these figures are exclusively based on the assumption that about 50% of 600,000 cardiovascular deaths occur suddenly. (Myerburg and Spooner, 2001; Danieli G A, 2006). Moreover, according to recent trials, up to 50% of the deaths in patients with coronary artery disease and left ventricular systolic dysfunction are sudden or arrhythmic in nature. (Cannom D S, 2006). While the incidence of sudden or arrhythmic deaths is lower in patients with heart failure due to non-ischemic aetiologies, there is currently no way to detect which heart failure patients will die from an arrhythmia rather than progressive left ventricle systolic dysfunction. Although certain clinical markers such as greater age, degree of left ventricle systolic dysfunction, and severity of heart failure can predict general mortality, there is low specificity in detecting the mode of death.
A healthy cardiac rhythm not only consists of a heart that beats at the proper pace, but the muscular contractions of the four chambers of the heart must also be properly mediated such that they can contract in a coordinated fashion. The heart has specialized conduction pathways in both the atria and the ventricles that enable the rapid conduction of excitation (i.e. depolarization) throughout the myocardium. Normally, the sinoatrial node (“SA node”) initiates each heart-beat cycle by depolarizing so as to generate an action potential. This action potential propagates relatively quickly through the atria, which react by contracting, and then relatively slowly through the atrio-ventricular node (“AV node”). From the AV node, activation propagates rapidly through the His-Purkinje system to the ventricles, which also react by contracting. This natural propagation synchronizes the contractions of the muscle fibers of each chamber and synchronizes the contraction of each atrium or ventricle with the contralateral atrium or ventricle.
The rate at which the SA node depolarizes determines the rate at which the atria and ventricles contract and thus controls the heart rate. The pace at which the SA node depolarizes is regulated by the autonomic nervous system which can alter the heart rate so that the heart, for instance, beats at a faster rate during exercise and beats at a slower rate during rest. The above-described cycle of events holds true for a healthy heart and is termed normal sinus rhythm.
The heart, however, may have a disorder or disease that results in abnormal activation that preempts sinus rhythm, and results in an irregular heartbeat, i.e. an arrhythmia. Individuals with cardiac ailments, and especially those at risk of SCD, may suffer from an irregular pace and/or uncoordinated mechanical activity wherein the myocardial depolarization and contraction of the chambers do not occur simultaneously. Without the synchronization afforded by the normally functioning specialized conduction pathways or the proper pacing by the SA node, the heart's pumping efficiency is greatly diminished and can thus compromise a patient's cardiac output. Several different factors may lead to the development of an arrhythmia, including atherosclerosis, thrombosis, defects in electrogenesis and nerve impulse propagation, influences of the sympathetic and parasympathetic systems, ischemia (inadequate oxygen supply to the cells due to lack of blood flow), and/or poor vascular control.
A variety of techniques are practiced to minimize the uncoordinated motion patients with cardiac ailments exhibit. Such current therapies can generally be divided into pharmacological, surgical, and electrical methods. While each of these therapies may be used individually, it is not uncommon for physicians to concurrently employ more than one. In addition, the physician's decision as to which type of therapy(ies) to employ depends, in large part, on the type of arrhythmia that the patient exhibits.
With respect to electrical therapy, catheter ablation and cardiac rhythm management devices have particularly evolved as the gold standard therapies for patients at high risk for ventricular and supraventricular tachyarrhythmia (i.e. abnormally rapid beating of the heart). Catheter ablation is an invasive procedure used to remove the faulty electrical pathways from the heart. The procedure consists of inserting several flexible catheters into the patient's blood vessels, typically into the femoral, internal jugular, or subclavian veins. The catheters are then advanced towards the heart and high-frequency electrical impulses are used to induce an arrhythmia, and then ablate (destroy) the abnormal tissue that is causing the arrhythmia. While catheter ablation of most arrhythmias has an extremely high success rate, the procedure is highly invasive and requires direct contact with the region of interest.
Cardiac rhythm management devices are implantable devices that provide electrical stimulation to selected chambers of the heart in order to treat cardiac rhythm disorders. There are numerous types of cardiac rhythm management devices, the most notable of which include pacemakers and implantable cardioverter defibrillator (“ICD”) devices.
A pacemaker is a cardiac rhythm management device that paces the heart with timed pacing pulses. The simplest configuration of a pacemaker is a power source with a timing circuit and an electrical lead designed to carry electrical energy to the heart. The most common condition for which pacemakers are used is in the treatment of bradycardia, where the ventricular rate is slow. Pacing therapy may also be applied in order to treat cardiac rhythms that are too fast, termed anti-tachycardia pacing.
If functioning properly, the pacemaker makes up for the heart's inability to pace itself at an appropriate rhythm by enforcing a normal heart rate. It does this by using electrical energy to cause the myocardium to contract when necessary, as determined based off of a normal sinus rhythm. Currently, pacemakers are capable of “dual-chamber pacing”, which initiates a contraction in the atrium, the ventricle, or both. When enough energy is sent down through the lead to cause depolarization in the myocardium, and therefore a contraction, “capturing” of the heart occurs and the depolarization effect can be observed on an electrocardiogram (“ECG”). As the term is used herein, “capture threshold” is the minimum amount of energy necessary to capture the heart.
An ECG of a normal sinus rhythm is characterized by a P wave, which corresponds with atrial depolarization and contraction of the atria, followed by the QRS complex, which corresponds with depolarization and contraction of the ventricles. Due to size differences between the atria and the ventricles, the P wave is considerably smaller than the QRS complex. A T wave follows the QRS complex and corresponds to ventricular repolarization. Atrial repolarization is difficult to detect with an ECG as the atrial repolarization signal has a small amplitude and is mainly hidden by the much larger QRST complex. In addition to the P wave and the QRST complex, a normal ECG is also characterized by a PR interval, defined as the time between atrial and ventricle contractions, of about 0.12 to 0.20 sections and regular R-R intervals, defined as the time between QRST complexes, of about 0.60 to 1 second.
The pacing rate of a pacemaker consists of the average number of pulses delivered from the power source over a specified period of time, usually one (1) minute. The length of time from one pacing impulse to the next is termed the pacing interval. It is the goal of using a pacemaker that the pacing interval eventually corresponds to the normal sinus rhythm discussed above. The pulse width, (measured in milliseconds), is the length of time that the current flows through the lead when the pacemaker delivers an energy pulse. Conventional pacemakers typically contain an internal timing clock to measure time in thousandths of a second, or milliseconds (ms), to ensure the pacing impulses are delivered correctly. The pacemaker's output is equal to the amount of energy delivered with each energy pulse. Energy can be considered as “voltage over time” or voltage at a certain pulse width. The optional capture thresholds can be calculated by varying the pulse width while maintaining a constant voltage.
Economically, cardiac pacemakers account for more than 50% of worldwide expenditure in the electrophysiology market, which includes cardiac pacemakers, ICDs, and radiofrequency ablation devices. (ANAES, 1999). In 1998, the percentage accounted for approximately $2.5 billion in sales, or approximately 540,000 implanted pacemakers. (ANAES, 1999). The number of cardiac pacemakers inserted continues to increase over time, especially in light of the ever-increasing elderly population.
Pacemaker implantation is a common surgical procedure that is performed under local anesthesia and requires only a short hospitalization time. A lead catheter is inserted into the chest, through the subclavian vein, which is located below the collarbone and above the heart. The pacemaker's leads are then threaded through the catheter and adhered to the appropriate chamber or chambers of the heart. The electrodes are typically positioned in contact with the inner surface of the right atrium or ventricle. The pacemaker's leads are then tested to guarantee that there is consistent capture with a sufficiently low energy level to ensure that the pacemaker can function properly over an extended period of time. Finally, a small pocket is created subcutaneously on the upper portion of the chest wall to hold the power source, which is thereafter closed with stitches. It is not uncommon for the power source—typically a conventional lithium battery—to be easily felt through the skin. Such lithium batteries typically exhibit a battery life of eight (8) to ten (10) years and are easily replaced by performing a relatively minor surgery where the subcutaneous pouch is reopened under local anesthesia.
A common problem with cardiac pacemaker implantation is dislocation of the leads, which typically occurs in 1.1% to 6% of all cases. (ANAES, 1999). This complication generally takes place within two (2) months of insertion and requires additional surgery to relocate the leads. In addition, the implantation of a pacemaker also carries the risks of developing haematoma, hemorrhage, perforations of the heart and the pleura, infection (more specifically, endocarditis), and symptomatic and asymptomatic venous thrombosis. Electrophysiological complications may also include pacemaker syndrome, an atrial fibrillation considered to be less common with single chamber atrial inhibited pacing mode cardiac pacemakers. In addition, the implantation procedure is invasive and requires direct contact with the region of interest.
In about 30% of chronic heart failure patients, the disease process compromises the myocardium's ability to contract, which thereby alters the conduction pathways through the heart and causes a delay in the beginning of right or left ventricular systole. (Abraham et al., 2002). On an ECG, such a desynchronization is manifested as a QRS complex interval lasting more than 120 ms. It has been proposed that intraventricular conduction delay may compromise the ability of the failing heart to eject blood and may consequently increase the severity of the mitral valve regurgitant flow. In patients with heart failure, the intraventricular conduction delay leads to clinical instability and an increased risk of death. These uncoordinated contractions cannot be remedied by a conventional pacemaker alone, as simple pacemakers merely address pacing issues. Currently, there are several devices that make use of atrial-synchronized biventricular pacing in order to coordinate right and left ventricular contraction.
A cardiac resynchronization therapy (“CRT”) device, also known as a biventricular pacemaker, is a type of pacemaker that can pace both ventricles (right and left) of the heart. As noted above, by pacing both sides of the heart, the pacemaker can resynchronize a heart that does not beat in synchrony, which is common in patients at risk for SCD. After the Food and Drug Administration approved CRT in 2001, approximately 271,000 heart failure patients in the United States have received CRT for moderate to severe heart failure. (Aranda et al., 2005).
Conventional CRT devices closely resemble pacemakers, except that a typical CRT device has three (3) electrical leads which are coupled to cardiac tissue. The first lead is typically coupled to the right atrium, a second lead is typically coupled to the right ventricle, and a third lead is typically coupled to the left ventricle (often via the coronary sinus or great vein). Implantation and maintenance of a CRT device are linked to greater risks than conventional pacemaker devices. This is because a device delivering CRT requires that the third lead is inserted through the coronary sinus and advanced into the cardiac vein to pace the left ventricle. As a result, the risk of an unsuccessful implantation of the device or even dissection or perforation of the coronary sinus or cardiac vein is increased significantly. Erroneous efforts to implant the third lead or the device may also have severe complications, including complete heart block, hemopericardium, and even cardiac arrest. In addition, it is not uncommon for the left ventricular lead to become dislodged during long-term pacing, which necessitates repositioning or replacement of the lead.
An additional cardiac rhythm management device that is closely related to a pacemaker is the ICD device. Like CRT, ICDs resemble pacemakers and are often used in the treatment of patients at risk for SCD. An ICD is a small, battery powered electrical impulse generator which is typically implanted in patients who are at risk of SCD due to ventricular fibrillation. The principles of cardiac arrhythmia detection and treatment are incorporated into the implantable device, such that the ICD can monitor the heart's sinus rhythm and deliver the proper electrical treatment automatically.
An ICD has the ability to treat many types of heart rhythm disturbances (including uncoordinated cardiac activity) by means of pacing, cardioversion, or defibrillation. ICDs are capable of constantly monitoring the rate and rhythm of the heart and delivering therapies, by way of electrical shock, when the heart activity is not in accordance with the optimal sinus rhythm. In this manner, ICDs are able to offer joined therapy with programmable anti-arrhythmia pacing schemes, as well as low and high energy shocks in multiple ranges of tachycardia rates. Conventional ICD devices are considerably smaller than the first prototypes of the early 1980s and can easily be positioned under the skin in the left chest. The majority ICD generators must be replaced every four (4) to five (5) years.
In the United States in 2002, 415,780 ICD devices were implanted. (Wilkoff B L, 2007). The process of implantation of an ICD is similar to implantation of a pacemaker. Similar to CRT devices, these devices typically include electrode leads which pass through the coronary sinus and into the cardiac vein. Accordingly, the same risks that apply to the implantation and maintenance of pacemakers, and specifically CRT devices, are applicable to ICD devices.
Due to the growing number of patients requiring some form of cardiac rhythm therapies, there is a need for a technique that benefits from the advantages of ICDs and pacemakers without suffering the problems associated with such devices. Furthermore, such novel techniques should be easy to understand and implement, universally adoptable, and have competitive advantages over conventional heart treatment devices, such as ICDs and pacemakers.
Articles discussing cardiac disease and treatment include:
Abraham W T et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002; 346(24):1845-1853.
Agence Nationale d′Accréditation et d'Évaluation en Santé. Evaluation clinique et économique des endoprothèses aortiques. Paris: ANAES; 1999.
Aranda et al. Management of heart failure after cardiac resynchronization therapy: integrating advanced heart failure treatment with optimal device function. J Am Coll Cardiol 2005; 46(12): 2193-98.
Cannom D S. “After DEFINITE, SCD-HeFT, COMPANION: Do We Need to Implant an ICD in All Patients With Heart Failure?” Cardiac Arrhythmias Proceedings of the 9th International Workshop on Cardiac Arrhythmias. A. Raviele. Venice 425-434 (2005).
Danieli G A. “Sudden Arrhythmic Death: Which Genetic Determinants?” Cardiac Arrhythmias Proceedings of the 9th International Workshop on Cardiac Arrhythmias. A. Raviele. Venice 385-392 (2005).
Myerburg R J, Spooner P M. Opportunities for sudden death prevention: directions for new clinical and basic research. Cardiovasc Res 2001; 50: 177-85.
Wilkoff B L. Pacemaker and ICD malfunction—an incomplete picture. JAMA 2007; 295(16): 1944-1946.